Novel ebselen-based building block for the solid phase synthesis of selenopeptides
4 affiliations
- 1Department of Organic Chemistry, Faculty of Sciences
- 2University of Granada
- 3Unit of Excellence in Chemistry Applied to Biomedicine and the Environment
- 4Biotechnology Institute
Abstract
Although some organic selenocompounds exhibit significant therapeutic potential, synthetic access to selenopeptides remains severely limited due to complex postassembly functionalizations strategies. To overcome these limitations, we developed a stable, ebselen-derived lysine compatible with standard Fmoc/tBu solid-phase peptide synthesis (SPPS). We synthesized the Fmoc-Lys(Ebs)-OH building block in five steps, characterizing it by HRMS and NMR spectroscopy. We then evaluated its chemical stability in standard SPPS conditions by assembling a test tripeptide and a diverse tetrapeptide library containing a variety of aminoacids. The novel Fmoc-Lys(Ebs)-OH demonstrated excellent coupling efficiency and high stability, tolerating repeated basic deprotections, couplings and strong acid cleavage to yield selenopeptides without degradation or byproducts. This novel building block enables the direct, site-specific incorporation of ebselen during SPPS, avoiding labor-intensive post-synthetic modifications to access to complex organoselenium peptides for biological and structure-activity relationship studies.
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BibTeX
@misc{lopezruiz2026novel,
title = {{Novel ebselen-based building block for the solid phase synthesis of selenopeptides}},
author = {Alejandro Lopez-Ruiz and Mariano Ortega-Muñoz and Fernando Hernandez-Mateo and F. Javier Lopez-Jaramillo and Alicia Megia-Fernandez},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15008326/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008326/v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Novel ebselen-based building block for the solid phase synthesis of selenopeptides
AU - Alejandro Lopez-Ruiz
AU - Mariano Ortega-Muñoz
AU - Fernando Hernandez-Mateo
AU - F. Javier Lopez-Jaramillo
AU - Alicia Megia-Fernandez
PY - 2026
DA - 2026/09/04
PB - ChemRxiv
DO - 10.26434/chemrxiv.15008326/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008326/v1
AB - Although some organic selenocompounds exhibit significant therapeutic potential, synthetic access to selenopeptides remains severely limited due to complex postassembly functionalizations strategies. To overcome these limitations, we developed a stable, ebselen-derived lysine compatible with standard Fmoc/tBu solid-phase peptide synthesis (SPPS). We synthesized the Fmoc-Lys(Ebs)-OH building block in five steps, characterizing it by HRMS and NMR spectroscopy. We then evaluated its chemical stability in standard SPPS conditions by assembling a test tripeptide and a diverse tetrapeptide library containing a variety of aminoacids. The novel Fmoc-Lys(Ebs)-OH demonstrated excellent coupling efficiency and high stability, tolerating repeated basic deprotections, couplings and strong acid cleavage to yield selenopeptides without degradation or byproducts. This novel building block enables the direct, site-specific incorporation of ebselen during SPPS, avoiding labor-intensive post-synthetic modifications to access to complex organoselenium peptides for biological and structure-activity relationship studies.
ER -